乙型肝炎病毒抑制肝癌细胞凋亡通过sponging microRNA 15a/16的集

StephenW

   Hepatitis B Virus Inhibits Apoptosis of Hepatoma Cells by Sponging the MicroRNA 15a/16 Cluster

    Ningning Liu a,b,
    Jinfang Zhang a,
    Tong Jiao a,b,
    Zhiwei Li c,
    Jirun Peng d,
    Zhuqingqing Cui d and
    Xin Ye a

- Author Affiliations

    Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, Chinaa
    Graduate University of Chinese Academy of Sciences, Beijing, Chinab
    302 Hospital of PLA, Beijing, Chinac
    Peking University People's Hospital, Beijing, Chinad

ABSTRACT

Hepatitis B virus (HBV) causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV persistence are not well understood. In this study, we found that HBV inhibited the chemotherapy drug etoposide-induced apoptosis of hepatoma cells. Further analysis revealed that HBV mRNAs possess a microRNA 15a/16 (miR-15a/16)-complementary site (HBV nucleotides [nt] 1362 to 1383) that acts as a sponge to bind and sequester endogenous miR-15a/16. Consequently, Bcl-2, known as the target of miR-15a/16, was upregulated in HBV-infected cells. The data from HBV-transgenic mice further confirmed that HBV transcripts cause the reduction of miR-15a/16 and increase of Bcl-2. More importantly, we examined the levels of HBV transcripts and miR-15a/16 in HBV-infected HCC from patients and found that the amount of HBV mRNA and the level of miR-15a/16 were negatively correlated. Consistently, the level of Bcl-2 mRNA was upregulated in HBV-infected patients. In conclusion, we identified a novel HBV mRNA–miR-15a/16–Bcl-2 regulatory pathway that is involved in inhibiting etoposide-induced apoptosis of hepatoma cells, which may contribute to facilitating chronic HBV infection and hepatoma development.
FOOTNOTES

        Received 7 August 2013.
        Accepted 25 September 2013.
    Address correspondence to Xin Ye, [email protected].

    Published ahead of print 2 October 2013

StephenW

乙型肝炎病毒抑制肝癌细胞凋亡通过海绵的microRNA 15a/16的集群

    宁宁刘A，B，
    锦芳张某，
    砼浇A，B，
    李志伟C，
    吉润鹏D，
    崔Zhuqingqing d和
    鑫叶一

- 作者所属机构

    中心分子免疫学，微生物研究所病原微生物与免疫院重点实验室，中国中国科学院（ CAS） ，北京，吃奶
    中国科学院，北京， Chinab研究生
    302医院，北京，解放军Chinac
    北京大学人民医院，北京， Chinad

摘要

乙型肝炎病毒（HBV）引起慢性肝炎，数百万​​世界各地的人，可能最终导致肝细胞癌（HCC ） 。 HBV持久性的分子机制尚不十分清楚。在这项研究中，我们发现，乙型肝炎病毒抑制化疗药物鬼臼乙叉甙肝癌细胞诱导细胞凋亡。进一步分析发现， HBV基因具有“的microRNA 15a/16 （ miR-15a/16 ）互补网站（ HBV核苷酸[ NT] 1362年至1383年），作为海绵结合和封存内源性miR-15a/16的。因此，上调Bcl-2蛋白，称为作为目标miR-15a/16 ，在HBV感染的细胞。 HBV转基因小鼠中的数据进一步证实，乙肝病毒转录导致的miR-15a/16增加Bcl-2的减少。更重要的是，我们在HBV感染的肝癌患者检查HBV转录水平和miR-15a/16和发现的HBV mRNA和miR-15a/16水平的量呈负相关。坚持，上调Bcl-2的表达水平在HBV感染的患者。总之，我们确定了新HBV mRNA-miR-15a/16-Bcl-2的监管途径抑制依托泊苷诱导肝癌细胞的凋亡，这可能有助于促进慢性HBV感染和肝癌发展中涉及。
脚注

        2013年8月7日收到的。
        接受2013年9月25日。
    地址对应鑫烨， [email protected] 。